The association between chronic renal failure and severe hyperlipidemia has been recognized for many years. Vascular disease of the atherosclerotic type is hastened. Observations in our laboratory have led us to hypothesize that there may be a most important connection between the plasma level of high density lipoproteins (HDL) and the level of circulating plasma very low density liprprotens (VLDL). Lewis et al (New Eng. J. Med. 20:1097, 1966) suggested that HDL levels are regualted by the kidney by some unknown mechanism. We have shown that HDL is the main carrier of "activator" peptides which are essential to the dydrolysis reaction catalyzed by lipoprotein lipase (Whayne and Felts, Circ. Res.